内皮细胞损伤及其功能障碍在动脉粥样硬化中作用的研究进展

doi:10.12114/j.issn.1007-9572.2024.0440

摘要/Abstract

摘要： 心血管疾病是具有高发病率和高死亡率的常见疾病。动脉粥样硬化（AS）是多种心血管疾病的病理基础，其主要表现为动脉血管壁的脂质堆积和斑块形成，影响周围组织或器官缺血或坏死。本文系统讨论内皮细胞（ECs）在AS中的作用，总结了其损伤和功能障碍机制以及在AS中与巨噬细胞、血管平滑肌细胞之间的相互作用。本文表明ECs在AS中起到至关重要的作用，减轻其损伤及功能障碍有助于减轻AS的发生、发展，以期为AS的治疗提供新的方案。

关键词: 动脉粥样硬化, 内皮细胞, 功能障碍, 能量代谢

Abstract:

Cardiovascular disease is a prevalent condition characterized by a high incidence rate and mortality. Atherosclerosis (AS) serves as the underlying pathological mechanism for numerous cardiovascular diseases, primarily marked by lipid accumulation and plaque formation within arterial walls, thereby impacting tissue or organ ischemia or necrosis. This comprehensive article delves into the pivotal role of endothelial cells (ECs) in atherosclerosis, elucidating their mechanisms of injury and dysfunction, as well as their interactions with macrophages and vascular smooth muscle cells (VSMCs) during this process. The findings presented herein underscore the critical involvement of ECs in AS pathogenesis, emphasizing that mitigating damage to these cells and preserving their functionality can potentially ameliorate the onset and progression of AS. Our aim is to provide novel therapeutic avenues for AS.

Key words: Atherosclerosis, Endothelial cells, Dysfunction, Energy metabolism

中图分类号:

R 543.5

高海钧,任佳禹,王若琳,等. 内皮细胞损伤及其功能障碍在动脉粥样硬化中作用的研究进展[J]. 中国全科医学, 2025, 28(21): 2697-2704. DOI: 10.12114/j.issn.1007-9572.2024.0440.
GAO Haijun,REN Jiayu,WANG Ruolin, et al. Research Progress on the Role of Endothelial Cell Injury and Dysfunction in Atherosclerosis[J]. Chinese General Practice, 2025, 28(21): 2697-2704. DOI: 10.12114/j.issn.1007-9572.2024.0440.

图/表 2

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ECs功能障碍		相关因子	作用机制	参考文献
炎症氧化应激		ROS	3'-唾液酸乳糖通过抑制超氧化物活性来抑制LPS诱导的ECs高通透性	[14]
		ROS	苯甲酰苯甲酮通过SIRT3-SOD2-mtROS通路改善线粒体功能障碍进而抑制炎症反应	[15,16,17]
		Nrf2	Nrf2的激活通过抑制ECs炎症和脂质过氧化来抑制AS	[18]
		NF-κB	PCSK9和Nogo B通过ECs的NF-κB通路调节AS	[19,20]
		NOX	Rab27a通过抑制NOX2和caspase-3表达来减少ECs氧化应激	[25]
		NOX	人参皂苷通过破坏NOX2复合物的组装减少了氧化应激和炎症反应	[26]
程序性死亡	凋亡	Nrf2 NF-κB	CD137信号通路可以通过Nrf2和NF-κB通路介导的促氧化和促炎机制促进ECs的凋亡	[28]
		内质网应激	胰岛素受体底物1和TMEM215（跨膜蛋白215）通过线粒体相关的内质网膜，调节ECs凋亡	[29,30]
		microRNAs	miR-106a-5p的下调可以缓解ox-LDL通过靶向STAT3引发的ECs损伤	[31]
		microRNAs	miR-122通过靶向XIAP促进ECs凋亡，从而加重AS	[32,33]
	焦亡	caspase-1	尼古丁通过ROS-NLRP3-caspase-1诱导ECs焦亡	[35,36]
		caspase-3 caspase-8	caspase-3和caspase-8通过切割GSDME和GSDMD蛋白介导凋亡	[37]
		cGAS-STING	IQGAP1通过cGAS-STING通路诱导ECs焦亡导致AS	[39]
		microRNAs	miR-635，miR-302c-3p，miR-455-5p通过调节NLRP3炎症小体的激活影响ECs焦亡	[41,42]
	铁死亡	AMPK	肾上腺髓质素通过抑制AMPK介导的ECs铁死亡来缓解AS	[46]
		Nrf2	GLXB和褪黑激素通过激活Nrf2通路抑制铁死亡来抑制AS	[47,48]
		p38/NCOA4	高剂量电离辐射通过调节p38/NCOA4介导的ECs铁死亡来加重AS	[49]
衰老		SIRT1 SIRT3 SIRT6	复方丹参滴丸通过SIRT1的激活减少了ECs的衰老	[54]
		SIRT1 SIRT3 SIRT6	PM2.5通过SIRT1/PGC-1α/SIRT3信号通路诱导ECs过早地衰老	[55]
		p53	YPEL2通过p53/p21途径调节ECs衰老和AS	[56]
		线粒体功能障碍	SGLT2抑制剂和西洛他唑减轻ECs炎症和线粒体功能障碍调节ECs衰老	[57,58]
剪切应力		层流	层流诱导暴露于IFN-γ的ECs的KLF2/4表达，抑制ECs增殖，对AS有保护作用	[64]
剪切应力		扰流	扰流诱导ROS的产生，刺激ECs增殖，创造了AS的环境	[65,66,67]

ECs功能障碍		相关因子	作用机制	参考文献
炎症氧化应激		ROS	3'-唾液酸乳糖通过抑制超氧化物活性来抑制LPS诱导的ECs高通透性	[14]
		ROS	苯甲酰苯甲酮通过SIRT3-SOD2-mtROS通路改善线粒体功能障碍进而抑制炎症反应	[15,16,17]
		Nrf2	Nrf2的激活通过抑制ECs炎症和脂质过氧化来抑制AS	[18]
		NF-κB	PCSK9和Nogo B通过ECs的NF-κB通路调节AS	[19,20]
		NOX	Rab27a通过抑制NOX2和caspase-3表达来减少ECs氧化应激	[25]
		NOX	人参皂苷通过破坏NOX2复合物的组装减少了氧化应激和炎症反应	[26]
程序性死亡	凋亡	Nrf2 NF-κB	CD137信号通路可以通过Nrf2和NF-κB通路介导的促氧化和促炎机制促进ECs的凋亡	[28]
		内质网应激	胰岛素受体底物1和TMEM215（跨膜蛋白215）通过线粒体相关的内质网膜，调节ECs凋亡	[29,30]
		microRNAs	miR-106a-5p的下调可以缓解ox-LDL通过靶向STAT3引发的ECs损伤	[31]
		microRNAs	miR-122通过靶向XIAP促进ECs凋亡，从而加重AS	[32,33]
	焦亡	caspase-1	尼古丁通过ROS-NLRP3-caspase-1诱导ECs焦亡	[35,36]
		caspase-3 caspase-8	caspase-3和caspase-8通过切割GSDME和GSDMD蛋白介导凋亡	[37]
		cGAS-STING	IQGAP1通过cGAS-STING通路诱导ECs焦亡导致AS	[39]
		microRNAs	miR-635，miR-302c-3p，miR-455-5p通过调节NLRP3炎症小体的激活影响ECs焦亡	[41,42]
	铁死亡	AMPK	肾上腺髓质素通过抑制AMPK介导的ECs铁死亡来缓解AS	[46]
		Nrf2	GLXB和褪黑激素通过激活Nrf2通路抑制铁死亡来抑制AS	[47,48]
		p38/NCOA4	高剂量电离辐射通过调节p38/NCOA4介导的ECs铁死亡来加重AS	[49]
衰老		SIRT1 SIRT3 SIRT6	复方丹参滴丸通过SIRT1的激活减少了ECs的衰老	[54]
		SIRT1 SIRT3 SIRT6	PM2.5通过SIRT1/PGC-1α/SIRT3信号通路诱导ECs过早地衰老	[55]
		p53	YPEL2通过p53/p21途径调节ECs衰老和AS	[56]
		线粒体功能障碍	SGLT2抑制剂和西洛他唑减轻ECs炎症和线粒体功能障碍调节ECs衰老	[57,58]
剪切应力		层流	层流诱导暴露于IFN-γ的ECs的KLF2/4表达，抑制ECs增殖，对AS有保护作用	[64]
剪切应力		扰流	扰流诱导ROS的产生，刺激ECs增殖，创造了AS的环境	[65,66,67]